Sequential eukaryotic translation initiation factor 5 (eIF5) binding to the charged disordered segments of eIF4G and eIF2ß stabilizes the 48S preinitiation complex and promotes its shift to the initiation mode.
Mol Cell Biol
; 32(19): 3978-89, 2012 Oct.
Article
em En
| MEDLINE
| ID: mdl-22851688
ABSTRACT
During translation initiation in Saccharomyces cerevisiae, an Arg- and Ser-rich segment (RS1 domain) of eukaryotic translation initiation factor 4G (eIF4G) and the Lys-rich segment (K-boxes) of eIF2ß bind three common partners, eIF5, eIF1, and mRNA. Here, we report that both of these segments are involved in mRNA recruitment and AUG recognition by distinct mechanisms. First, the eIF4G-RS1 interaction with the eIF5 C-terminal domain (eIF5-CTD) directly links eIF4G to the preinitiation complex (PIC) and enhances mRNA binding. Second, eIF2ß-K-boxes increase mRNA binding to the 40S subunit in vitro in a manner reversed by the eIF5-CTD. Third, mutations altering eIF4G-RS1, eIF2ß-K-boxes, and eIF5-CTD restore the accuracy of start codon selection impaired by an eIF2ß mutation in vivo, suggesting that the mutual interactions of the eIF segments within the PIC prime the ribosome for initiation in response to start codon selection. We propose that the rearrangement of interactions involving the eIF5-CTD promotes mRNA recruitment through mRNA binding by eIF4G and eIF2ß and assists the start codon-induced release of eIF1, the major antagonist of establishing tRNA(i)(Met)mRNA binding to the P site.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Saccharomyces cerevisiae
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RNA Fúngico
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Fator de Iniciação 2B em Eucariotos
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Proteínas de Saccharomyces cerevisiae
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Fator de Iniciação 5 em Eucariotos
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Fator de Iniciação Eucariótico 4G
Idioma:
En
Revista:
Mol Cell Biol
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Estados Unidos